We have recently developed a general synthetic method whereby the C-D ring system of the cardiac aglycones can be constructed. Our method involves acid-catalyzed cyclization of a suitable olefinic epoxide, and should be applicable to a wide variety of compounds. With this model work finished, we are beginning the total synthesis of representative cardenolides and bufadienolides, compounds which are known for their cardiotonic cytotoxic properties. We have also developed a general synthesis of Beta-substituted butenolides, and plan to examine the method in detail.